Phase Separation and Transcription Regulation: Are Super-Enhancers and Locus Control Regions Primary Sites of Transcription Complex Assembly?
Open accessAbstract
It is proposed that the multiple enhancer elements associated with locus control regions and super‐enhancers recruit RNA polymerase II and efficiently assemble elongation competent transcription complexes that are transferred to target genes by transcription termination and transient looping mechanisms. It is well established that transcription complexes are recruited not only to promoters but also to enhancers, where they generate enhancer RNAs. Transcription at enhancers is unstable and frequently aborted. Furthermore, the Integrator and WD‐domain containing protein 82 mediate transcription termination at enhancers. Abortion and termination of transcription at the multiple enhancers of locus control regions and super‐enhancers provide a large pool of elongation competent transcription complexes. These are efficiently captured by strong basal promoter elements at target genes during transient looping interactions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Current theories propose liquid-liquid phase separation and some form of transcription factor trapping or engagement of transcription factors in multivalent interactions independent of assembly into phase-separated liquid-like droplets.
“current theories propose liquid-liquid phase separation18,64–66 and some form of TF trapping22,67 or engagement of TFs in multivalent interactions independent of assembly into phase-separated liquid-like droplets.68”
From Super-enhancers include classical enhancers and facilitators to fully activate gene expression (2023) · cites this paper as [66]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 86 · Cited by 41
Research works printed but not linked: 85
- [1]Vernimmen D, Bickmore WA, Trends Genet 2015, 31, 696. 26599498
- [2]Medina-Rivera A, Santiago-Algarra D, Puthier D, Spicuglia S, Trends Biochem Sci 2018, 43, 452. 29673772
- [3]Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME, Nature 2010, 465, 182. 20393465 PMC3020079
- [4]De Santa F, Barozzi I, Mietton F, Ghisletti S, Polletti S, Tusi BK, Muller H, Ragoussis J, Wei CL, Natoli G, PLoS Biol 2010, 8, e1000384. 20485488 PMC2867938
- [5]Kim TK, Shiekhattar R, Cell 2015, 162, 948. 26317464 PMC4556168
- [6]Beagrie RA, Pombo A, Bioessays 2016, 38, 881. 27452946
- [7]Bulger M, Groudine M, Cell 2011, 144, 327. 21295696 PMC3742076
- [8]Felsenfeld G, Groudine M, Nature 2003, 421, 448. 12540921
- [9]Zentner GE, Scacheri PC, J Biol Chem 2012, 287, 30888. 22952241 PMC3438921
- [10]Yang W, Ernst P, Curr Opin Hematol 2017, 24, 322. 28375985 PMC5603181
- [11]Mikhaylichenko O, Bondarenko V, Harnett D, Schor IE, Males M, Viales RR, Furlong EEM, Genes Dev 2018, 32, 42. 29378788 PMC5828394
- [12]Andersson R, Refsing Andersen P, Valen E, Core LJ, Bornholdt J, Boyd M, Heick Jensen T, Sandelin A, Nat Commun 2014, 5, 5336. 25387874
- [13]Grzechnik P, Tan-Wong SM, Proudfoot NJ, Trends Biochem Sci 2014, 39, 319. 24928762 PMC4085477
- [14]Lai F, Gardini A, Zhang A, Shiekhattar R, Nature 2015, 525, 399. 26308897 PMC4718573
- [15]Austenaa LM, Barozzi I, Simonatto M, Masella S, Della Chiara G, Ghisletti S, Curina A, de Wit E, Bouwman BA, de Pretis S, Piccolo V, Termanini A, Prosperini E, Pelizzola M, de Laat W, Natoli G, Mol Cell 2015, 60, 460. 26593720
- [16]Henriques T, Scruggs BS, Inouye MO, Muse GW, Williams LH, Burkholder AB, Lavender CA, Fargo DC, Adelman K, Genes Dev 2018, 32, 26. 29378787 PMC5828392
- [17]Price DH, Proc Natl Acad Sci U S A 2018, 115, 4810. 29691322 PMC5949015
- [18]Palstra RJ, Tolhuis B, Splinter E, Nijmeijer R, Grosveld F, de Laat W, Nat Genet 2003, 35, 190. 14517543
- [19]Carter D, Chakalova L, Osborne CS, Dai YF, Fraser P, Nat Genet 2002, 32, 623. 12426570
- [20]Benabdallah NS, Bickmore WA, Cold Spring Harb Symp Quant Biol 2015, 80, 45. 26590168
- [21]Deng W, Lee J, Wang H, Miller J, Reik A, Gregory PD, Dean A, Blobel GA, Cell 2012, 149, 1233. 22682246 PMC3372860
- [22]Kagey MH, Newman JJ, Bilodeau S, Zhan Y, Orlando DA, van Berkum NL, Ebmeier CC, Goossens J, Rahl PB, Levine SS, Taatjes DJ, Dekker J, Young RA, Nature 2010, 467, 430. 20720539 PMC2953795
- [23]Fukaya T, Lim B, Levine M, Cell 2016, 166, 358 27293191 PMC4970759
- [24]Lim B, Curr Opin Biotechnol 2018, 52, 49. 29501816 PMC6082720
- [25]Bartman CR, Hsu SC, Hsiung CC, Raj A, Blobel GA, Mol Cell 2016, 62, 237. 27067601 PMC4842148
- [26]Gu B, Swigut T, Spencley A, Bauer MR, Chung M, Meyer T, Wysocka J, Science 2018, 359, 1050. 29371426 PMC6590518
- [27]Engel JD, Tanimoto K, Cell 2000, 100, 499. 10721987
- [28]Li Q, Peterson KR, Fang X, Stamatoyannopoulos G, Blood 2002, 100, 3077. 12384402 PMC2811695
- [29]Grosveld F, van Assendelft GB, Greaves DR, Kollias G, Cell 1987, 51, 975. 3690667
- [30]Tuan D, Solomon W, Li Q, London IM, Proc Natl Acad Sci U S A 1985, 82, 6384. 3879975 PMC390720
- [31]Forrester WC, Takegawa S, Papayannopoulou T, Stamatoyannopoulos G, Groudine M, Nucleic Acids Res 1987, 15, 10159. 3480506 PMC339937
- [32]Bungert J, Davé U, Lim KC, Lieuw KH, Shavit JA, Liu Q, Engel JD, Genes Dev 1995, 9, 3083. 8543153
- [33]Milot E, Strouboulis J, Trimborn T, Wijgerde M, de Boer E, Langeveld A, Tan-Un K, Vergeer W, Yannoutsos N, Grosveld F, Fraser P, Cell 1996, 87, 105. 8858153
- [34]Navas PA, Peterson KR, Li Q, Skarpidi E, Rohde A, Shaw SE, Clegg CH, Asano H, Stamatoyannopoulos G, Mol Cell Biol 1998, 18, 4188. 9632803 PMC109003
- [35]Bender MA, Ragoczy T, Lee J, Byron R, Telling A, Dean A, Groudine M, Blood 2012, 119, 3820. 22378846 PMC3335386
- [36]Hu X, Bulger M, Bender MA, Fields J, Groudine M, Fiering S, Blood 2006, 107, 821. 16189270 PMC1895626
- [37]Allahyar A, Vermeulen C, Bouwman BAM, Krijger PHL, Verstegen MJAM, Geeven G, van Kranenburg M, Pieterse M, Straver R, Haarhuis JHI, Jalink K, Teunissen H, Renkens IJ, Kloosterman WP, Rowland BD, de Wit E, de Ridder J, de Laat W, Nat Genet 2018, 50, 1151. 29988121
- [38]Tuan D, Kong S, Hu K, Proc Natl Acad Sci U S A 1992, 89, 11219. 1454801 PMC50521
- [39]Leach KM, Nightingale K, Igarashi K, Levings PP, Engel JD, Becker PB, Bungert J, Mol Cell Biol 2001, 21, 2629. 11283243 PMC86894
- [40]Johnson KD, Christensen HM, Zhao B, Bresnick EH, Mol Cell 2001, 8, 465. 11545748
- [41]Routledge SJ, Proudfoot NJ, J Mol Biol 2002, 323, 601. 12419253
- [42]Levings PP, Bungert J, Eur J Biochem 2002, 269, 1589. 11895428
- [43]Liang S, Moghimi B, Yang TP, Strouboulis J, Bungert J, J Cell Biochem 2008, 105, 9. 18500726 PMC2696286
- [44]Pott S, Lieb JD, Nat Genet 2015, 47, 8. 25547603
- [45]Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, Hoke HA, Young RA, Cell 2013, 155, 934. 24119843 PMC3841062
- [46]Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA, Cell 2013, 153, 307. 23582322 PMC3653129
- [47]Huang J, Li K, Cai W, Liu X, Zhang Y, Orkin SH, Xu J, Yuan GC, Nat Commun 2018, 9, 943. 29507293 PMC5838163
- [48]Shin HY, Willi M, HyunYoo K, Zeng X, Wang C, Metser G, Hennighausen L, Nat Genet 2016, 48, 904. 27376239 PMC4963296
- [49]Sabari BR, Dall’Agnese A, Boija A, Klein IA, Coffey EL, Shrinivas K, Abraham BJ, Hannett NM, Zamudio AV, Manteiga JC, Li CH, Guo YE, Day DS, Schuijers J, Vasile E, Malik S, Hnisz D, Lee TI, Cisse II, Roeder RG, Sharp PA, Chakraborty AK, Young RA, Science 2018, 361, eaar3958 29930091 PMC6092193
- [50]Soutourina J, Nat Rev Mol Cell Biol 2018, 19, 262. 29209056
- [51]Nozawa K, Schneider TR, Cramer P, Nature 2017, 545, 248. 28467824
- [52]Kuras L, Borggrefe T, Kornberg RD, Proc Natl Acad Sci U S A 2003, 100, 13887. 14623974 PMC283516
- [53]Jeronimo C, Langelier MF, Bataille AR, Pascal JM, Pugh BF, Robert F, Mol Cell 2016, 64, 455. 27773677 PMC5824718
- [54]Wong KH, Jin Y, Struhl K, Mol Cell 2014, 54, 601. 24746699 PMC4035452
- [55]Jeronimo C, Robert F, Nat Struct Mol Biol 2014, 21, 449. 24704787 PMC3997488
- [56]D’Urso A, Takahashi YH, Xiong B, Marone J, Coukos R, Randise-Hinchliff C, Wang JP, Shilatifard A, Brickner JH, Elife 2016, 5. PMC4951200 27336723
- [57]Zaborowska J, Egloff S, Murphy S, Nat Struct Mol Biol 2016, 23, 771. 27605205
- [58]Chesnut JD, Stephens JH, Dahmus ME, J Biol Chem 1992, 267, 10500. 1316903
- [59]Akoulitchev S, Mäkelä TP, Weinberg RA, Reinberg D, Nature 1995, 377, 557. 7566158
- [60]Yamaguchi Y, Shibata H, Handa H, Biochim Biophys Acta 2013, 1829, 98. 23202475
- [61]Mayfield JE, Burkholder NT, Zhang YJ, Biochim Biophys Acta 2016, 1864, 372. 26779935 PMC4761483
- [62]Lynch CJ, Bernad R, Calvo I, Nóbrega-Pereira S, Ruiz S, Ibarz N, Martinez-Val A, Graña-Castro O, Gómez-López G, Andrés-León E, Espinosa Angarica V, Del Sol A, Ortega S, Fernandez-Capetillo O, Rojo E, Munoz J, Serrano M, Cell Rep 2018, 22, 396. 29320736 PMC5775503
- [63]Chong S, Dugast-Darzacq C, Liu Z, Dong P, Dailey GM, Cattoglio C, Heckert A, Banala S, Lavis L, Darzacq X, Tjian R, Science 2018, 361, eaar2555 29930090 PMC6961784
- [64]Cho WK, Spille JH, Hecht M, Lee C, Li C, Grube V, Cisse II, Science 2018, 361, 412. 29930094 PMC6543815
- [65]Lu H, Yu D, Hansen AS, Ganguly S, Liu R, Heckert A, Darzacq X, Zhou Q, Nature 2018, 558, 318. 29849146 PMC6475116
- [66]Boehning M, Dugast-Darzacq C, Rankovic M, Hansen AS, Yu T, Marie-Nelly H, McSwiggen DT, Kokic G, Dailey GM, Cramer P, Darzacq X, Zweckstetter M, Nat Struct Mol Biol 2018, 25, 833. 30127355
- [67]Kwon I, Kato M, Xiang S, Wu L, Theodoropoulos P, Mirzaei H, Han T, Xie S, Corden JL, McKnight SL, Cell 2013, 155, 1049. 24267890 PMC4010232
- [68]Hnisz D, Shrinivas K, Young RA, Chakraborty AK, Sharp PA, Cell 2017, 169, 13. 28340338 PMC5432200
- [69]Eychenne T, Novikova E, Barrault MB, Alibert O, Boschiero C, Peixeiro N, Cornu D, Redeker V, Kuras L, Nicolas P, Werner M, Soutourina J, Genes Dev 2016, 30, 2119. 27688401 PMC5066617
- [70]Bruzzone MJ, Grünberg S, Kubik S, Zentner GE, Shore D, Genes Dev 2018, 32, 1252. 30108132 PMC6120713
- [71]Catarino RR, Stark A, Genes Dev 2018, 32, 202. 29491135 PMC5859963
- [72]Carey LB, van Dijk D, Sloot PM, Kaandorp JA, Segal E, PLoS Biol 2013, 11, e1001528. 23565060 PMC3614515
- [73]Tantale K, Mueller F, Kozulic-Pirher A, Lesne A, Victor JM, Robert MC, Capozi S, Chouaib R, Bäcker V, Mateos-Langerak J, Darzacq X, Zimmer C, Basyuk E, Bertrand E, Nat Commun 2016, 7, 12248. 27461529 PMC4974459
- [74]Rienzo M, Casamassimi A, Biochim Biophys Acta 2016, 1859, 1269. 27427483
- [75]Carlsten JO, Zhu X, Gustafsson CM, Trends Biochem Sci 2013, 38, 531. 24074826
- [76]Sawado T, Halow J, Bender MA, Groudine M, Genes Dev 2003, 17, 1009. 12672691 PMC196035
- [77]Stamatoyannopoulos G, Exp Hematol 2005, 33, 259. 15730849 PMC2819985
- [78]Barrow JJ, Li Y, Hossain M, Huang S, Bungert J, Nucleic Acids Res 2014, 42, 4363. 24497190 PMC3985677
- [79]Vieira KF, Levings PP, Hill MA, Crusselle VJ, Kang SH, Engel JD, Bungert J, J Biol Chem 2004, 279, 50350. 15385559 PMC3705557
- [80]Zhou Z, Li X, Deng C, Ney PA, Huang S, Bungert J, J Biol Chem 2010, 285, 15894. 20236933 PMC2871457
- [81]Li G, Ruan X, Auerbach RK, Sandhu KS, Zheng M, Wang P, Poh HM, Goh Y, Lim J, Zhang J, Sim HS, Peh SQ, Mulawadi FH, Ong CT, Orlov YL, Hong S, Zhang Z, Landt S, Raha D, Euskirchen G, Wei CL, Ge W, Wang H, Davis C, Fisher-Aylor KI, Mortazavi A, Gerstein M, Gingeras T, Wold B, Sun Y, Fullwood MJ, Cheung E, Liu E, Sung WK, Snyder M, Ruan Y, Cell 2012, 148, 84. 22265404 PMC3339270
- [82]Cook PR, Science 1999, 284, 1790. 10364545
- [83]Ghamari A, van de Corput MP, Thongjuea S, van Cappellen WA, van Ijcken W, van Haren J, Soler E, Eick D, Lenhard B, Grosveld FG, Genes Dev 2013, 27, 767. 23592796 PMC3639417
- [84]Schoenfelder S, Sexton T, Chakalova L, Cope NF, Horton A, Andrews S, Kurukuti S, Mitchell JA, Umlauf D, Dimitrova DS, Eskiw CH, Luo Y, Wei CL, Ruan Y, Bieker JJ, Fraser P, Nat Genet 2010, 42, 53. 20010836 PMC3237402
- [85]Bintu B, Mateo LJ, Su JH, Sinnott-Armstrong NA, Parker M, Kinrot S, Yamaya K, Boettiger AN, Zhuang X, Science 2018, 362, eaau1783. 30361340 PMC6535145
- Authors
- Gurumurthy, A., Shen, Y., Gunn, E. M., & Bungert, J.
- Affiliations
- University of Florida (US)
- Corresponding author
- Bungert, Jörg
- Venue
- BioEssays
- Publisher
- Wiley
- Published
- 2018-11-30
- Volume
- 41
- Issue
- 1
- Pages
- e1800164-e1800164
- ISSN
- 0265-9247 (ISSN-L)
- 1521-1878
- PMC
- PMC6484441
- OpenAlex
- W2903161951
- Cited by
- 41
- References
- 86
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2022: 9 · 2021: 10 · 2020: 8 · 2019: 5
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-02-08)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- BioEssays (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (RO1DK52356)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- super-enhancers, locus control region, enhancer RNA, transcription termination, RNA polymerase II, transcription complex assembly, enhancer looping, Integrator complex, enhancer-promoter interactions
- MeSH terms
- Enhancer Elements, Genetic, Gene Expression Regulation, Humans, RNA Polymerase II, Transcription, Genetic, Locus Control Region, beta-Globins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review